Nitrones reaction mechanisms

Many nitrones and nitroso-compounds have been exploited as spin traps in elucidating radical reaction mechanisms by EPR spectroscopy (Section 3.5.2.1). The initial adducts are nitroxides which can trap further radicals (Scheme 5.17). 

Reductive Cross-Coupling of Nitrones Recently, reductive coupling of nitrones with various cyclic and acyclic ketones has been carried out electrochem-ically with a tin electrode in 2-propanol (527-529). The reaction mechanism is supposed to include the initial formation of a ketyl radical anion (294), resulting from a single electron transfer (SET) process, with its successive addition to the C=N nitrone bond (Scheme 2.112) (Table 2.9). 

It was demonstrated (83) that the reaction of dinitrostyrenes (28) with aryl diazo compounds RR CN2 afford nitronates (24 g) in good yields. These products contain the nitro group at the C-4 atom in the trans position with respect to the substituent at C-5 (if R =H). Since the reaction mechanism remains unknown, the direct formation of cyclic nitronates (24 g) from pyrazolines A without the intermediate formation of cyclopropanes also cannot be ruled out. 

The above dramatic dependence of regio- and stereoselectivity on the nature of the metal can be explained by the reaction mechanism shown in Scheme 11.49 (167). The nitrone cycloadditions of allylic alcohols are again magnesium-specific just like the nitrile oxide reactions described in Section 11.2.2. Magnesium ions accelerate the reaction through a metal ion-bound intramolecular cycloaddition path. On the other hand, zinc ions afford no such rate acceleration, but these ions catalyze the acetalization at the benzoyl carbonyl moiety of the nitrone to provide a hemiacetal intermediate. The subsequent intramolecular regio- and stereoselective cycloaddition reaction gives the observed products. 

The reaction mechanism involves silylation of a nitro group oxygen followed by deprotonation to give the intermediate silyl nitronate 137, which undergoes 1,3-dipolar cycloaddition to give the product 136 in excellent yields and with diastereomeric excess ratios often exceeding 99 1 (Scheme 15). 

RSaS stereoisomers.29 The 1,3-dipolar cycloaddition of [60]fullerene with diazomethane, nitrile oxide, and nitrone afforded fullereno-pyrazolines and -isoxazolines. These reactions were modelled at the B3LYP/6-31G(d,p)//AMl level and the reaction mechanisms, regiochemistry, and nature of addition were investigated.30... 

The following reaction mechanism was ruled out by the authors cited [4 + 2] cycloaddition of the diene with the nitrone to give tertiary amine oxide, 7-21, which then thermally rearranges to the product. (Thermal rearrangement of a tertiary amine oxide to an alkylated hydroxylamine is called a Meisenheimer rearrangement.)... 

Attempted reactions of 7d with Ru3(CO)i2 in order to isolate a possible nitrene complex intermediately formed were unsuccessful [9], Thus, we can only speculate about the reaction mechanism. Formation of a nitrene complex analogous to compound 4 is a reasonable hypothesis. However, when the carbonylation of some organic nitro derivatives was conducted in c/.y-cyclooctene as solvent and with Ru3(CO)i2 as catalyst, nitrones have been detected among the products [14]. Under these conditions, the intermediate nitroso derivative reacts with the alkene solvent to yield the corresponding nitrone. The reaction of nitroso derivatives with alkenes is in fact one of the methods for the preparation of nitrones [28]. Thus it could be that in the case of the carbonylation of ortho-nitrostyrenes, the reaction follows the path depicted in Scheme 4 ... 

Ligation of nitriles to a metal center changes features of the reaction mechanism. In the case of metal-free reactions, the mechanism is concerted and highly synchronous, that is, the reaction occurs in one step via formation of one cyclic flve-membered transition state (TS), and the changes of chemical bonds directly involved in the process take place simultaneously. The estimated degree of asynchronicity of the reactions between nitrones and uncomplexed nitriles is only 5-15% [43, 45-48]. In contrast, the coordination of nitriles to the metal (Pt or Pd) results in a dramatic increase of the reaction asynchronicity to 19-49%, and, in some cases, the TS of the reaction may become acyclic [47]. At the same time, the global mechanism of the DCA usually remains concerted. 

The mechanism is presumed to involve a pathway related to those proposed for other base-catalyzed reactions of isocyanoacetates with Michael acceptors. Thus base-induced formation of enolate 9 is followed by Michael addition to the nitroalkene and cyclization of nitronate 10 to furnish 11 after protonation. Loss of nitrous acid and aromatization affords pyrrole ester 12. 

A model for the mechanism of the highly enantioselective AlMe-BINOL-cata-lyzed 1,3-dipolar cycloaddition reaction was proposed as illustrated in Scheme 6.13. In the first step nitrone la coordinates to the catalyst 11b to form intermediate 12. In intermediate 13, which is proposed to account for the absolute stereoselectivity of this reaction, it is apparent that one of the faces of the nitrone, the si face, is shielded by the ligand whereas the re face remains available... 

A mechanism for this reaction has been proposed [75], The first key intermediate in the reaction is the copper(I) acetylide 42. The additional ligand may be solvent or H2O. The acetylene moiety in 42 is activated for a 1,3-dipolar cycloaddition with the nitrone to give intermediate 43, with introduction of chirality in the product. A possible route to ris/traws-41 might be via intermediate 44. Finally, the cis isomer is isomerized into the thermally more stable trans-41. It should be mentioned that the mechanism outlined in Scheme 6.32 was originally proposed for a racemic version of the reaction to which water was added. 

Scheme 3.20. Proposed mechanism of asymmetric nitro-aldol reactions catalyzed by LLB, LLB-II, or LLB-LI nitronate...

Although these reactions are formulated as ionic reactions via 947 and 949, because of the apparent partial formation of polymers and inhibition of the fluoride-catalyzed reaction of pyridine N-oxide 860 with aUyl 82 or benzyltrimethylsilane 83 by sulfur or galvinoxyl yet not by Tempo, a radical mechanism caimot be excluded [61, 62]. The closely related additions of allyltrimethylsilane 82 (cf. Section 7.3) to nitrones 976 are catalyzed by TMSOTf 20 to give, via 977, either o-unsatu-rated hydroxylamines 978 or isoxazoHdines 979 (cf also the additions of 965 to 962a and 969 in schemes 7.20 and 7.21). 

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